Opiate receptors are members of the large class of seven transmembrane spanning helical proteins that are coupled to G proteins. The G proteins, in turn, control the activity of adenylyl cyclase and several ion channels. We seek to understand in detail the mechanism of action of receptors for the opioid peptides and their close relatives. The neuroblastoma x glioma hybrid cell line, NG108-15, is richly endowed with opiate receptors, and is a particularly good source of this protein since it expresses only the delta type of opiate receptor. We and others, have cloned the delta opiate receptor of NG108-15 cells, which is the best characterized of this class. In the brain, the gene is expressed at low levels in many regions but transcripts are found in particularly large amounts in the anterior pituitary and pineal glands. Since these tissues are located outside the blood brain barrier, opioid peptides easily can reach receptors in these areas from the blood. The presence of many opiate receptors in these readily accessible organs can therefore be of great physiological interest. The opiate receptors in bovine and rat pineal are found to be almost completely occupied with natural ligands, presumably peptides, but when these are removed a large number of receptors can be measured. Opiate antagonists decrease the rate of production of melatonin by pineal cells. Since this process is known to be cAMP dependent, opiate agonists may be stimulating cAMP production. We have now obtained direct evidence for an increase in cAMP levels in pineal cell membranes caused by stimulation of their opiate receptors. This is a highly unusual activity for opiate receptor which, in most tissues, reduce cAMP levels by inhibiting adenylyl cyclase. We have also succeeded in expressing a functional delta opioid receptor in E. coli. as a fusion protein with the maltose binding protein. This fusion protein can be extracted from the membranes with detergent and purified.